The cat neuromuscular preparation uniquely developed by the Cornell group has enabled the analysis of drug actions on mammalian motor nerve terminals in vivo. These techniques will be used to study denervation. Functional and pharmacologic changes in presynaptic behavior furnish a remarkably sensitive index of the earliest changes in denervation and in this way, the role of cellular metabolism, neural activity, trophic transport and key membrane components will be ascertained. Means of retarding early denervation changes will be sought. Motor nerve terminals have also been found a prime site of injury in the neuropathy syndrome of delayed organophosphate poisoning. Because of the growing importance of this environmental hazard, it is intended to resolve the molecular and functional events that lead to the disabling of motor nerve terminals. Results already indicate that this early subtle injury can be detected by simple testing, applicable clinically, and therefore might be used to evaluate exposed persons. Certain corticosteroids have been found to increase the facilitatory function of motor nerve. An attempt will be made to define where in the neuron this action occurs, the nature of the action (i.e., membranal or metabolic) and the usefulness of corticosteroid treatment in the toxic neuropathies. Other toxic neuropathies (e.g., isoniazid, vinca alkaloids, lead, acrylamide) will be studied and compared to the functional derangements of OP neuropathy to determine whether specific functional disorders of motor nerve signal particular lesions.